1cet: Difference between revisions

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[[Image:1cet.jpg|left|200px]]
[[Image:1cet.png|left|200px]]


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==Overview==
{{ABSTRACT_10187806}}
Although the molecular mechanism by which chloroquine exerts its effects on the malarial parasite Plasmodium falciparum remains unclear, the drug has previously been found to interact specifically with the glycolytic enzyme lactate dehydrogenase from the parasite. In this study we have determined the crystal structure of the complex between chloroquine and P. falciparum lactate dehydrogenase. The bound chloroquine is clearly seen within the NADH binding pocket of the enzyme, occupying a position similar to that of the adenyl ring of the cofactor. Chloroquine hence competes with NADH for binding to the enzyme, acting as a competitive inhibitor for this critical glycolytic enzyme. Specific interactions between the drug and amino acids unique to the malarial form of the enzyme suggest this binding is selective. Inhibition studies confirm that chloroquine acts as a weak inhibitor of lactate dehydrogenase, with mild selectivity for the parasite enzyme. As chloroquine has been shown to accumulate to millimolar concentrations within the food vacuole in the gut of the parasite, even low levels of inhibition may contribute to the biological efficacy of the drug. The structure of this enzyme-inhibitor complex provides a template from which the quinoline moiety might be modified to develop more efficient inhibitors of the enzyme.


==About this Structure==
==About this Structure==
1CET is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CET OCA].  
1CET is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CET OCA].  
==Reference==
Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase., Read JA, Wilkinson KW, Tranter R, Sessions RB, Brady RL, J Biol Chem. 1999 Apr 9;274(15):10213-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10187806 10187806]
[[Category: L-lactate dehydrogenase]]
[[Category: L-lactate dehydrogenase]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
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[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Tricarboxylic acid cycle]]
[[Category: Tricarboxylic acid cycle]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 12:39:16 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:07:49 2008''

Revision as of 14:07, 26 June 2008

File:1cet.png

Template:STRUCTURE 1cet

CHLOROQUINE BINDS IN THE COFACTOR BINDING SITE OF PLASMODIUM FALCIPARUM LACTATE DEHYDROGENASE.


Template:ABSTRACT 10187806

About this Structure

1CET is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 17:07:49 2008

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